1. Field of the Invention
This invention relates to compositions such as those used for coating implantable medical devices such as stents.
2. Description of Related Art
Stents are used not only as a mechanical intervention but also as a vehicle for providing biological therapy. As a mechanical intervention, stents act as scaffoldings, functioning to physically hold open the wall of the passageway. Stents are capable of being compressed, so that they can be inserted through small lumens via catheters, and then expanded to a larger diameter once they are at the desired location. Biological therapy for reducing or eliminating thrombosis or restenosis can be achieved by medicating the stents. Medicated stents provide for the local administration of a therapeutic substance at the diseased site. In order to provide an efficacious concentration to the treated site, systemic administration of such medication often produces adverse or toxic side effects for the patient. Local delivery is a preferred method of treatment in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Local delivery thus produces fewer side effects and achieves more favorable results.
Local delivery can be accomplished by coating the stent with a polymeric carrier containing a biologically active agent. A polymer dissolved in an organic solvent and the agent added thereto are applied to the stent and the organic solvent is allowed to evaporate, leaving a polymeric coating impregnated with the agent.
In the development of drug eluting stents, the rate of release of an active agent from a stent is an important factor which needs to be evaluated. However, the rate of release of agents that have limited solubility in water and are unstable under ambient conditions is difficult to measure. One example of a drug that has proven to be effective for the treatment of restenosis but difficult to calculate the eluting rate from a stent is everolimus (40-O-(2-hydroxy)ethyl-rapamycin) (Novartis Corp.). everolimus, (40-O-(3-hydroxy)propyl-rapamycin, or 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin) are structural derivatives of rapamycin. Rapamycin is an immunosuppressive drug and also possesses antiproliferative properties. Everolimus has a very limited solubility in water, and is, in addition, quite unstable under ambient conditions, posing a serious obstacle for the study of the drug's release kinetics from a stent. In addition, everolimus has limited stability in an aqueous medium.
In view of the foregoing, there is a need to be able to solubilize these types of drugs, and more particularly everolimus, in water and to stabilize these drugs so as to prevent the drugs from degradation in an aqueous environment. Embodiments of the present invention disclose aqueous systems that meet these needs.